Distinct expression and inhibitory function of B and T lymphocyte attenuator on human T cells.
Distinct expression and inhibitory function of B and T lymphocyte attenuator on human T cells.
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DOI：
10.1111/j.1399-0039.2006.00710.x
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发表时间：
2007-02
期刊：
影响因子：
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通讯作者：
X. Wang;Y-J Chen;Q. Wang;Y. Ge;Q. Dai;Keya Yang;Fang-Xie;Y-H Zhou;Y. Hu;Y. Mao;X.-G. Zhang
中科院分区：
文献类型：
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作者：
X. Wang;Y-J Chen;Q. Wang;Y. Ge;Q. Dai;Keya Yang;Fang-Xie;Y-H Zhou;Y. Hu;Y. Mao;X.-G. Zhang
B和T淋巴细胞衰减因子（BTLA）是最近发现的一种新的CD 28超家族抑制性受体，与细胞毒性T淋巴细胞活化抗原（CTLA）-4和程序性死亡（PD）-1具有相似性。BTLA在T淋巴细胞上的结合可以显著降低T细胞受体（TCR）介导的活化。在这项研究中，我们产生了四个单克隆抗体（mAb）对人类BTLA。利用所制备的mAb 8H 9，发现BTLA分子在许多免疫细胞亚群上明确表达，并显示出调节性表达，这与其在T细胞活化过程中独特的配体疱疹病毒进入介体（HVEM）一致。另外，肺癌患者胸水中CD 4（+）和CD 8（+）T细胞中BTLA的表达增加。此外，我们发现BTLA诱导的负信号可以被mAb 7 D 7触发。BTLA与mAb 7 D 7的交联抑制T淋巴细胞增殖，下调T细胞活化标志物CD 25的表达，并抑制干扰素（IFN）-γ、白细胞介素（IL）-2、IL-4和IL-10的产生。
B and T lymphocyte attenuator (BTLA) has been recently identified as a new inhibitory receptor of the CD28 superfamily, with similarities to cytotoxic T lymphocyte activation antigen (CTLA)-4 and programmed death (PD)-1. Engagement of BTLA on T lymphocytes can profoundly reduce the T cell receptor (TCR)-mediated activation. In this study, we generated four monoclonal antibodies (mAbs) against human BTLA. Using the produced mAb 8H9, the BTLA molecule was found to distinctly express on many subgroups of immunocytes and show a regulatory expression, which was in accordance with its unique ligand herpes virus entry mediator (HVEM) in the process of T cell activation. In addition, the expression of BTLA was increased in the CD4(+) and CD8(+) T cells of pleural fluid in lung cancer patients. Furthermore, we showed that the BTLA-induced negative signals could be triggered by mAb 7D7. Cross-linking of BTLA with mAb 7D7 suppressed T lymphocyte proliferation, downregulated the expression of T cell activation marker CD25, and inhibited the production of interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10.